brain-endocrine-stress review

8/7/2019 Brain-Endocrine-Stress Review

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BrainBrain--EndocrineEndocrine--StressStressReviewReview

The HPA axisThe HPA axis



HPA axisHPA axis

PVN

Anterior

Pituitary

Adrenal

Gland

Cortisol

-ve

-ve

CRF

ACTH



CRFCRF Regulates basal and stressRegulates basal and stress--inducedinduced

release of pituitary ACTHrelease of pituitary ACTH

Detected in cerebral cortex,Detected in cerebral cortex,

hypothalamus, anterior pituitary,hypothalamus, anterior pituitary,adrenal glands, testis, ovary, gut,adrenal glands, testis, ovary, gut,heart, and lungsheart, and lungs

Three homologus neuropeptidesThree homologus neuropeptides Urcortin I, Urcortin II, and Urcortin IIIUrcortin I, Urcortin II, and Urcortin III

CRF gene expression can be alteredCRF gene expression can be altered(catecholamines, serotonin, cytokines,(catecholamines, serotonin, cytokines,

glucocorticoids)glucocorticoids)



CRFCRF--continuedcontinued

CRF R1CRF R1

Corticotrophs of the anterior pituitaryCorticotrophs of the anterior pituitary

Mediates actions of the HPA axis andMediates actions of the HPA axis andanxietyanxiety--related behaviorrelated behavior

CRF R2CRF R2

Brain and peripheryBrain and periphery

Regulation of feeding behavior andRegulation of feeding behavior andcardiovascular functioncardiovascular function



POMCPOMC

Proopiomelanocortin (POMC)Proopiomelanocortin (POMC)

Binding of CRF with CRF R1 onBinding of CRF with CRF R1 oncorticotrophscorticotrophs

Simulation of POMC mRNA synthesisSimulation of POMC mRNA synthesis

ACTH releaseACTH release



Actions of glucocorticoidsActions of glucocorticoids

Two receptorsTwo receptors

Mineralocorticoid receptorsMineralocorticoid receptors

Hippocampus and sensory and motor nuclei outsideHippocampus and sensory and motor nuclei outsidethe hypothalamusthe hypothalamus

Regulation of basal expression of ACTH, CRF and AVPRegulation of basal expression of ACTH, CRF and AVP

Glucocorticoid receptorsGlucocorticoid receptors Hypothamic PVN, brainstem catecholaminergic cellHypothamic PVN, brainstem catecholaminergic cell

groups, amygdala, hippocampus, pituitarygroups, amygdala, hippocampus, pituitary

Termination of the HPA axis response to stressTermination of the HPA axis response to stress



Actions of glucocorticoidsActions of glucocorticoids

Fetal organ maturation (esp. lungs)Fetal organ maturation (esp. lungs)

Metabolism (stimulatesMetabolism (stimulatesgluconeogenesis)gluconeogenesis)

Immune system (antiImmune system (anti--inflammatory,inflammatory,immunosuppression)immunosuppression)

Maintain vascular toneMaintain vascular tone



Regulators of the HPARegulators of the HPA

axisaxis Cytokines (leukemiaCytokines (leukemia--inhibitory factor (LIF),inhibitory factor (LIF),

interleukininterleukin--6 (IL6 (IL--6)6)

Stimulatory on POMC gene expression and ACTHStimulatory on POMC gene expression and ACTHexpressionexpression

Vasopressin (AVP)Vasopressin (AVP)

Potentates the effects of CRF on ACTH releasePotentates the effects of CRF on ACTH release

Chronic stressChronic stress

NoradrenalineNoradrenaline



Negative feedNegative feed--backback

Mediated by glucocorticoids at theMediated by glucocorticoids at thelevel of the pituitary andlevel of the pituitary and

hypothalamushypothalamus

Two phasesTwo phases

Rapid feedback (inhibition of CRF andRapid feedback (inhibition of CRF and

ACTH release)ACTH release) Delayed (down regulation of CRF andDelayed (down regulation of CRF and

POMC gene expression)POMC gene expression)



Circadian rhythmicityCircadian rhythmicity

Supraoptic nucleus (SCN)Supraoptic nucleus (SCN)

Peak glucocorticoids just before activePeak glucocorticoids just before activeperiodperiod

CRF requiredCRF required



HPA axis and stressHPA axis and stress

responseresponse Acute stressAcute stress

Systemic and neurogenicSystemic and neurogenic

Short term, enhanced secretion of ACTH andShort term, enhanced secretion of ACTH andglucocorticoidsglucocorticoids

Immunological stressImmunological stress

Stimulation by inflammatory cytokines (ILStimulation by inflammatory cytokines (IL--1, IL1, IL--

6, TNF6, TNF--EE

Repeated stressRepeated stress




HPA axis and stressHPA axis and stress

responseresponse Repeated stressRepeated stress

HabituationHabituation




QuestionsQuestionsFulford and Harbuz, 2005Fulford and Harbuz, 2005

1.1. What are the two systems that cause an endocrine response toWhat are the two systems that cause an endocrine response tostress?stress?

2.2. What peptides are synthesized in the parvocellular cells?What peptides are synthesized in the parvocellular cells?3.3. What are the differences between rapid and delayed feedback?What are the differences between rapid and delayed feedback?4.4. What are the 2 corticosteroid receptors and how do their functionsWhat are the 2 corticosteroid receptors and how do their functions

differ?differ?5.5. Give examples of afferent regulation of the HPA axis.Give examples of afferent regulation of the HPA axis.6.6. What are the two main categories of acute stress? GiveWhat are the two main categories of acute stress? Give

examples.examples.7.7. What effect does injecting animals with Lipopolysaccaride have onWhat effect does injecting animals with Lipopolysaccaride have on

cytokine production and on the HPA axis?cytokine production and on the HPA axis?8.8. Name some measures that can be used to evaluate an acute orName some measures that can be used to evaluate an acute or

chronic stress response.chronic stress response.9.9. How are endogenous opioids involved in the regulation of the HPAHow are endogenous opioids involved in the regulation of the HPA

axis?axis?10.10. What other factors are involved in the stress response?What other factors are involved in the stress response?



QuestionsQuestionsAbel and Majzoub, 2005Abel and Majzoub, 2005

1.1. Describe the HPA axis.Describe the HPA axis.2.2. What is POMC?What is POMC?3.3. In what regions of the body has CRF mRNA beingIn what regions of the body has CRF mRNA being

detected?detected?4.4. What are the 2 CRF receptors and where are theyWhat are the 2 CRF receptors and where are they

distributed?distributed?5.5. What peptide is required for normal diurnal pattern of What peptide is required for normal diurnal pattern of

glucocorticoids?glucocorticoids?6.6. What is the importance of maternally derivedWhat is the importance of maternally derived

glucocorticoids?glucocorticoids?7.7. Describe an experimental design using knockDescribe an experimental design using knock--out miceout mice

to study the effects of CRF on anxiety behavior.to study the effects of CRF on anxiety behavior.

brain-endocrine-stress review

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